The focal adhesion targeting sequence is the major inhibitory moiety of Fak-related non-kinase

Focal adhesion kinase (FAK) plays an important role in integrin-mediated si gnal transduction pathways and its C-terminal noncatalytic domain Fak-relat ed non-kinase (FRNK), which is autonomously expressed, acts as an inhibitor of FAK. A model has been proposed where FAK and FRNK compete for an essent ial common binding protein. A FRNK variant in which the direct interaction with v-Crk-associated tyrosine kinase substrate (CAS) was disturbed by poin t mutations still functioned as an inhibitor of FAK, suggesting that FRNK i s unlikely to inhibit FAK by sequestering CAS. Deletion variants of FRNK wi thin the region N-terminal to the focal adhesion targeting (FAT) sequence w ere still able to inhibit FAK function, indicating that this region is disp ensable for the inhibitory effect of FRNK. Overexpression of a green fluore scent protein (GFP) fusion protein containing the FAT sequence delayed cell spreading and reduced FAK tyrosine phosphorylation. This indicates that th e FAT sequence is the major inhibitory moiety within FRNK. (C) 2001 Elsevie r Science Inc. All rights reserved.